The goal of our investigation is to identify and to solve immunological problems in fetal pancreas transplantation in allogeneic recipients. The initial studies in the genetically defined rat model will include; (1) to attempt to suppress host immunereaction against donor antigens by specific immunotherapies to prolong fetal pancreas allograft survivals. An induction of specific unresponsiveness to donor antigens (suppressor T-cell mediated) and specific immunosuppression by active or passive enhancement will be tested in various donor-recipient combinations, (2) to verify the use of nude mice as an in vivo culture system for xenogenic fetal pancreases by comparing growth and development of fetal pancreases cultured in nude mice to those cultured in syngeneic recipients, (4) to identify effect of anti-insulin antibodies or autoimmunity to islet cells on allograft functions, and (5) to monitor tumor incidence in long surviving fetal pancreas recipients. The subsequent studies will be carried out in the dog model. The protocol of the studies will follow those designed for human fetal pancreas transplantation. (1) to evaluate a use of fetal thymus cells for DL-A typing and for mixed lymphocyte culture assays, (2) to determine the optimal fetal age for donors by measuring insulin and pancreatic enzyme contets and by monitoring growth and development of pancreases in nude mice, (3) to develop a cryopreservation procedure for storing pancreases and to test viability and function of freeze-thawed tissues, and lastly, (4) to evaluate effectiveness of specific immunotherapy most effective in prolonging rat pancreas allograft survivals and to demonstrate feasivility of freeze-thawed pancreas allografts for reversal of diabetes. We believe that the proposed investigation is an essential step to proceed in our investigation to demonstrate the feasibility of fetal pancreas transplants for reversal of Diabetes in human beings.